This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to examine how ongoing acute and chronic infections and exposure to tumors affect na[unreadable]ve bystander T cell populations. During the reporting period, we continued our studies analyzing the status, kinetics, and stability of na[unreadable]ve T cells during acute and chronic infections and to determine how chronic antigen exposure during persistent infections or persisting tumors has on the ability of bystander na[unreadable]ve T cells to mount immune responses. We also worked to determine the effect of introducing therapeutic cytokines during a chronic infection or tumor model has on bystander na[unreadable]ve T cells. Using a TCR transgenic model we exposed, by adoptive transfer, OVA TCR na[unreadable]ve T cells to acute LCMV infection or Lewis Lung Carcinoma tumor transplant model, recovered OVA na[unreadable]ve cells then determine their ability to respond to OVA infection. We have found that na[unreadable]ve T cells are affected by their environment and loose the ability to respond to their cognate antigen. In addition we have found that bystander na[unreadable]ve T cells exposed to an unrelated chronic environment progressively loose their ability to form stable memory populations when they encounter their cognate antigen in an intact animal. We will continue to work to develop clues in the timing of therapies that will lead to therapeutic developments for targeting na[unreadable]ve T cell viability during chronic diseases and immune suppression.